This subproject will continue to investigate cellular correlates of motivation and cognition in nonhuman primates as they relate to influences of cocaine on performance and behavior under different training paradigms. The subproject has established the means to record single and multiple single unit activity in different brain regions while rhesus macaque monkeys are engaged in complex behavioral and cognitive tasks. The first task is a Go-Nogo paradigm in which both juice and cocaine are utilized as reinforcers for either initiating or withholding responses to specific stimuli within the trial. There are three variations of reward conditions that are employed in the task each testing a different aspect of juice vs cocaine rewarded responding. Neuronal activity is recorded from the ventral and dorsal striatum, frontal cortex and substantia nigra/VTA complex in monkeys that are well trained to perform the tasks. In the ventral striatai area we have found that neurons segregate into distinct classes to encode all the features of the task, including specific neurons that encode trials on which cocaine is the reinforcer and not those trials in which juice is delivered. The second major task is a cognitive test of shortterm memory in which stimuli are presented in a delayed-match-to-sample paradigm. Monkeys are trained to respond to identify a sample object from 2-6 other stimuli in the match phase at delays of 1-30 sec. Performance decreases both as a function of length of delay and number of items to choose from during the match phase of the task. Neurons are recorded from the hippocampal formation and frontal cortex and juice or cocaine presented as rewards on a trial-to- trial basis. Changes in discharge pattem as a function of cocaine vs juice reinforcement will be assessed. In addition, the effects of long-term exposure to cocaine (100 days) in the above two types of behavioral paradigms will be assessed with respect to changes in firing patterns of neurons with task-relevant firing tendencies. Monkeys will be withdrawn for a period of 30 or 60 days and saline delivered instead of cocaine on drug rewarded trials to extinguish prior task-associated cues. After withdrawal, cocaine reinstatement will be implemented in which drug trials (and the original stimuli associated with drug rewards) will be re-invoked. Alterations in neuronal firing patterns of identified cell types in the above structures will be assessed relative to initial exposure to cocaine to determine changes in system sensitivity following long-term exposure.